This is the second stage of the LoC system designed for cancer risk prediction. The design of a optimized droplet generator and a magnetic based CTC separator is presented through this research. The droplets which encapsulate circulating tumor cells have more magnetic particles compared to the blood droplets which does not contain CTCs (more information). Therefore the droplets can be separated using a magnetic field. The magnetic and fluid co-simulation is performed using Ansys Fluent and Ansys Magnetostatic software.
Introduction
Circulating tumor cells (CTCs) are rare cells present in the blood of cancer patients. They are shed from both primary and metastatic tumors and are believed to play a key role in cancer progression. CTCs can serve as indicators of metastatic disease and possibly recurrence after surgery in some tumor types. The CTC count has been reported to correlate with overall tumor burden, and hence CTCs have been proposed as a tool for monitoring disease progression and response to therapy. Another major advantage of CTCs is that they can be further interrogated after detection. For example, sequencing of the genome and transcriptome could reveal mutations or quantitate gene expression. The detected cells also have the potential to be cultured, grown and tested with different combinations of chemotherapeutic agents for drug discovery and personalized medicine. Finally, increasing amounts of data suggest that cancer is a very heterogeneous disease.
Through this research I am trying to develop a system that integrates a microchip with a specially designed microfluidic flow to perform high throughput immunomagnetic separation for detection of CTC cells. The detection strategy is as illustrated in Figure 1.
Figure 1: overall system of the LoC device
The antibody conjugated magnetic beads are first incubated with the blood sample that might contain CTCs. The incubation is performed by the use of a micromixer specially designed to obtain the required mixing ration between blood and magnetic beads (more information). Depending on the average size of the CTC which is around 20 microns a droplet generator is designed to generate droplets which can encapsulate a CTC if those cells are available in the blood sample. Then the droplets flow in a microfluidic channel while a magnetic field is introduced at the end of the micro-channel to apply a vertical attractive force on the magnetic beads. If a droplet contains a CTC there are more magnetic particles which increase the droplet attraction towards the magnet while the droplets with normal blood cells are washed away to the normal blood droplet chamber under the effect of high flow rate.
Geometry and Meshing
There are two main focus areas in this research. First focus is on optimizing the droplet generator design to obtain the desired size droplets. The initial microfluidic design which was published through my previous research obtained the desired diameter to ensure that a droplet can encapsulate a single CTC. But the droplet velocities are high to be used in a magnetic separator. The boundary conditions and the model parameter are as illustrated in Figure 2.
Figure 2: Boundary conditions and the methods used
Numerical Model
Time dependent governing equations are solved in a CFD solver (ANSYS 18.1) based on a finite volume method. PISO algorithm is used to resolve the pressure-velocity coupling in momentum equation. The spatial derivatives are discretized using quadratic upstream interpolation for convective kinetics (QUICK) scheme. To avoid spurious currents as a result of mismatch between pressure and surface tension force discretization, the pressure staggering option (PRESTO) is employed for pressure interpolation. The geometric reconstruction scheme is adopted to solve the volume fraction equation. Second order implicit method is applied for discretization of temporal derivatives.
There were limitations in droplet formation depending on the geometry of the droplet generator. Therefore, droplet formation of several geometries were analysed to select the most suitable geometry.
The droplet formation of the finalized geometry and Pressure distribution and velocity profile results are as shown in the following contour plots.
Figure 3: Blood volume fraction, Pressure distribution and velocity profile
I am currently improving the optimization process and working on the co simulation for magnetic separation and looking forward to publish the results. More information will be added after the publication.
Supervised by :
Comments